Enhanced learning by posttrial injection of H1-but not H2-histaminergic antagonists into the nucleus basalis magnocellularis region

The aim of this study was to examine the effects of histaminergic antagonists on memory upon injection into the region of the nucleus basalis magnocellularis (NBM). In experiment 1, rats with chronically implanted cannulae were trained on the uphill avoidance task, which involves a punishment of a high-probability turning response on a tilted platform (negative geotaxis). Immediately after the training trial, that is, after a tail shock was administered upon performing the response, rats received one microinjection (0.5 microliter) of H1-receptor blocker chlorpheniramine (dose range 0.1 to 20 microgram) or the H2-receptor blocker ranitidine (same dose range) or saline into the NBM region. When tested 24 h later, rats treated with chlorpheniramine (20 micrograms) had significantly longer uphill latencies than vehicle controls and ranitidine-treated animals, indicative of superior learning of the avoidance response. In experiment 2, a test for possible proactive effects of posttrial chlorpheniramine on performance during the retention trial was performed. Animals were injected with either 20 micrograms chlorpheniramine or saline immediately after the training trial of the uphill task. One chlorpheniramine control group was treated with a delay of 5 h. Additional groups which received chlorpheniramine or vehicle after the training trial but no trail shock were included. When tested 24 h later, rats injected with 20 micrograms chlorpheniramine again exhibited significantly longer uphill latencies than did vehicle-injected rats. Retention latencies for the rats of the chlorpheniramine 5-h delayed group did not differ from those of the vehicle-injected rats, ruling out proactive effects of chlorpheniramine on performance. In summary, the histaminergic H1-blocker chlorpheniramine can enhance mnemonic functioning in addition to its reinforcing effects upon NBM injection as reported previously.     

趋近和回避动机的区分及其对心理病理学的影响

趋近和回避是动机的两种最基本形式, 反映着个体与环境的相互作用方式, 是个体适应环境的核心机能。回避动机保证了个体的生存, 趋近动机则促进个体的成长。两类动机系统在前额叶皮层呈不对称偏侧化分布, 趋近动机与左侧额叶皮层激活相连, 回避动机与右侧额叶皮层激活相连。Youngstorm 和Izard等认为两类动机系统失调可能与一系列的情绪和行为问题有关, 如躁狂、抑郁、焦虑和儿童多动症等。这一观点已得到一些相关研究和临床研究证实。建议未来研究关注趋近-回避动机区分与情绪和认知功能研究的融合, 进一步检验趋近-回避动机系统失调模型, 并加强趋近和回避动机系统的可塑性研究。     

年幼儿童的尺寸匹配误差现象

近十年来,尺寸匹配误差作为年幼儿童生活中的一种常见的尺寸误用现象逐渐受到了一些研究者的关注。现有研究主要集中在尺寸匹配误差的特点、出现频率和产生原因等方面。抑制控制的失败、神经通路的协调失败、“计划-控制”模型和“感觉-行动”模型、功能性推理偏好以及身体意识发展的不成熟等观点能够对某些类型的尺寸匹配误差现象做出解释。未来的研究应从进一步深入探讨尺寸匹配误差与假装的区别、完善研究方法以及跨文化研究的开展几方面进行。     

Ethanol state-dependent memory: involvement of dorsal hippocampal muscarinic and nicotinic receptors

In the present study, the effects of bilateral injections of cholinergic agents into the hippocampal CA1 regions (intra-CA1) on ethanol state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Pre-training intraperitoneal injection (i.p.) of ethanol (0.25, 0.5 and 1 g/kg) dose dependently induced impairment of memory retention. Pre-test administration of ethanol (0.5 and 1 g/kg, i.p.) induced state-dependent retrieval of the memory acquired under pre-training ethanol (1 g/kg, i.p.) influence. Pre-test intra-CA1 injection of physostigmine (2.5 and 5 μg/mouse, intra-CA1) or nicotine (0.3 and 0.5 μg/mouse, intra-CA1) improved pre-training ethanol (1 g/kg)-induced retrieval impairment. Moreover, pre-test administration of physostigmine (2.5 and 5 μg/mouse, intra-CA1) or nicotine (0.3 and 0.5 μg/mouse, intra-CA1) with an ineffective dose of ethanol (0.25 g/kg) significantly restored the retrieval and induced ethanol state-dependent memory. Pre-test intra-CA1 injection of the muscarinic receptor antagonist, atropine (4 and 8 μg/mouse, intra-CA1) or the nicotinic receptor antagonist, mecamylamine (2 and 4 μg/mouse, intra-CA1) 5 min before the administration of ethanol (1 g/kg, i.p.) dose dependently inhibited ethanol state-dependent memory. Pre-test intra-CA1 administration of physostigmine (0.5, 2.5 and 5 μg/mouse), atropine (2, 4 and 8 μg/mouse), nicotine (0.1, 0.3 and 0.5 μg/mouse) or mecamylamine (1, 2 and 4 μg/mouse) alone cannot affect memory retention. These findings implicate the involvement of a dorsal hippocampal cholinergic mechanism in ethanol state-dependent memory and also it can be concluded that there may be a cross-state dependency between ethanol and acetylcholine.     

Rigidity in social and emotional memory in the R6/2 mouse model of Huntington's disease

Four experiments were conducted to examine social and emotional memory in the R6/2 transgenic mouse model of Huntington’s disease. First, R6/2 mice were tested in a social transmission of food preference task where they had to acquire a preference for a flavoured food (acquisition) and subsequently to learn a preference for a different flavour (shifted reinforcement). R6/2 mice performed well in the acquisition trial. However, they were impaired in the shifted reinforcement trial and perseverated on the first preference learned. Second, mice were trained in an inhibitory avoidance paradigm, with either one or two footshocks delivered during the training. WT mice given one footshock showed retention levels lower than those of mice trained with two footshocks. By contrast, there was no difference in retention levels of R6/2 mice given either one or two footshocks. Third, mice were tested in an active avoidance task that paired a mild footshock with a warning light. R6/2 mice had a strong age-dependent deficit in this task. Finally, mice were tested in a conditioned taste aversion task that paired a saccharine solution with a nausea-inducing agent (LiCl). R6/2 mice displayed normal aversion, however this was not extinguished following repeated exposure to saccharine solution alone. Our data show that while R6/2 mice have functional hippocampus-based memory, they have deficits in striatum-based memory skills. Further, social and emotional memories appear to be encoded in a rigid way that is not influenced by subsequent learning or by arousal levels.     

Upregulation of hippocampal TrkB and synaptotagmin is involved in treadmill exercise-enhanced aversive memory in mice

Cognitive functions usually involve various synaptic proteins and neurotrophic factors in the hippocampus. However, whether treadmill exercise can improve learning and memory by upregulating some of these molecules remain unraveled. To address this question, male BALB/c mice were divided into control and exercise groups, the latter group went through 4 weeks of treadmill exercise training. At the end of exercise training period, they were either tested for passive avoidance (PA) performance or sacrificed for quantifying the hippocampal levels of brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB, the BDNF receptor), synaptotagmin (a Ca²⁺-dependent synaptic vesicle protein), and SNAP-25 (a presynaptic vesicular fusion protein). Our results showed that treadmill exercise training (1) increased the retention latency without affecting the fear acquisition in the PA test, (2) transiently increased the hippocampal BDNF level at 1, 2, and 4 h after the completion of exercise training, and (3) persistently increased the hippocampal protein levels of full-length TrkB, phosphorylated TrkB and synaptotagmin, but not truncated TrkB or SNAP-25. Moreover, the protein expression level of full-length TrkB or synaptotagmin was positively correlated with PA performance in mice. Finally, inhibition of TrkB signaling by K252a abolished the exercise-facilitated PA performance and upregulation of TrkB and synaptotagmin. Taken together, these data suggest that the upregulation of TrkB and synaptotagmin in the hippocampus contributes to the exercise-facilitated aversive memory.     

Avoidance of timeout from response-independent food: effects of delivery rate and quality

In three experiments, a rat's lever presses could postpone timeouts from food pellets delivered on response-independent schedules. In Experiment 1, the pellets were delivered at variable-time (VT) rates ranging from VT 0.5 to VT 8 min. Experiment 2 replicated the VT 1 min and VT 8 min conditions of Experiment 1 with new subjects. Finally, subjects in Experiment 3 could postpone timeouts from delivery of pellets that differed in quality rather than quantity (unsweetened versus sweetened pellets). In general, response rates and success in avoiding increased as a function of the rate and quality of the pellets. Also, performance efficiency increased as the experiments progressed, that is, the avoidance response occurred later and later in the response-timeout interval. The results support the conclusion that timeout from reinforcement has functional properties similar to those of more commonly studied aversive stimuli (e.g., shock).     

学习困难儿童在工作记忆任务中抑制机制的研究

本研究的目的旨在探讨在WM任务中,LD儿童是否存在抑制机制缺陷。实验程序采用重复启动范式,设计“预期”和“目标”两种启动条件,随后通过间接测量的方式(内隐记忆测验)分别测得LD儿童和NLD儿童对预期词和目标词的启动量。结果表明,LD儿童对预期词的启动分数与目标词没有显著差异,NLD儿童对目标词的启动分数显著高于对预期词的启动分数。我们得出结论:在工作记忆任务中,LD儿童存在抑制机制缺陷。     

两类数学学习困难小学儿童抑制控制水平的实验研究

为考察单纯型数学困难与混合型数学困难小学儿童的抑制控制水平及特点,使用Stroop色词命名测验和颜色匹配反转作业,对各30名的单纯型困难、混合型困难和对照组小学儿童的优势反应抑制能力进行测试、分析。结果发现:单纯型数学困难儿童抑制优势反应的能力显著低于对照组,但其对事物初次学习的能力与对照组相当;混合型数学困难儿童在对事物初次学习能力及对优势反应的抑制能力方面均显著低于对照组儿童,其中对事物的初次学习能力也显著低于单纯型数学困难儿童。     

Electrical stimulation of the pedunculopontine tegmental nucleus in freely moving awake rats: time- and site-specific effects on two-way active avoidance conditioning

The pedunculopontine tegmental nucleus (PPTg) is involved in the regulation of thalamocortical transmission and of several functions related to ventral and dorsal striatal circuits. Stimulation of the PPTg in anesthetized animals increases cortical arousal, cortical acetylcholine release, bursting activity of mesopontine dopaminergic cells, and striatal dopamine release. It was hypothetized that PPTg stimulation could improve learning by enhancing cortical arousal and optimizing the activity of striatal circuits. We tested whether electrical stimulation (ES) of the PPTg, applied to freely-moving awake rats previously implanted with a chronic electrode, would improve the acquisition and/or the retention of two-way active avoidance conditioning, and whether this effect would depend on the specific PPTg region stimulated (anterior vs posterior) and on the time of ES: just before (pre-training) or after (post-training) each of three training sessions. The treatment consisted of 20 min of ES (0.2 ms pulses at 100 Hz; current intensity: 40-80 microA). The results showed that (1) this stimulation did not induce either any signs of distress nor abnormal behaviors, apart from some motor stereotyped behaviors that disappeared when current intensity was lowered; (2) pre-training ES applied to the anterior PPTg improved the acquisition of two-way active avoidance, (3) no learning improvement was found after either post-training ES of the anterior PPTg, or pre- and post-training ES of the posterior PPTg. The results give support to a role of PPTg in learning-related processes, and point to the existence of functional PPTg regions.